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The Loss of MCP‐1 Attenuates Cutaneous Ischemic‐reperfusion Injury
Author(s) -
Hasegawa Minoru,
Saito Yuki,
Fujimoto Manabu,
Takehara Kazuhiko,
Steeber Douglas A,
Sato Shinichi
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.730.4
Subject(s) - proinflammatory cytokine , chemokine , infiltration (hvac) , inflammation , monocyte , apoptosis , nitric oxide synthase , tumor necrosis factor alpha , medicine , nitric oxide , cancer research , chemistry , immunology , biochemistry , materials science , composite material
The formation of pressure ulcers is dependent on multiple factors including ischemic‐reperfusion (IR). This study assessed the mechanism of a previously reported murine model of cutaneous IR injury. Three cycles of IR (day 1–3) by external application of two magnetic plates were performed to induce pressure ulcer formation. Increased infiltration of neutrophils and macrophages, and augmented expression of proinflammatory cytokines and inducible nitric oxide synthase (iNOS), were observed during IR cycles. In this model, monocyte chemoattractant protein‐1 (MCP‐1) was remarkably increased at day 1 in the skin followed by inflammatory cell infiltration. Therefore, IR cycles were performed in MCP‐1 deficient (MCP‐1−/−) mice to evaluate the role of this chemokine in pressure ulcer development. MCP‐1−/− mice showed reduced macrophage infiltration and expression of tumor necrosis factor‐alpha and iNOS during IR cycles leading to attenuated apoptosis and skin injury. Importantly, MCP‐1 played a role in apoptosis and injury via inducing iNOS during the reperfusion rather than the ischemic period. These findings indicate that MCP‐1 may be a critical factor for macrophage recruitment and subsequent skin inflammation and injury during IR cycles. We propose that this is a useful model for investigating the mechanism of pressure ulcer formation using various transgenic mice.